A review on transfer factor an immune modulator
Department of Biochemistry, Periyar University, Salem 11, Tamil Nadu, India
Received 19 March 2013
Accepted 30 April 2013
Cell mediated immunity
Aim: To understand what is transfer factor and its signiﬁcance in stimulating immune
system which is necessary for the general maintenance of health.
Methods: Articles were collected from net sources.
Results: Basics, mechanism of action, safety aspects of transfer factor were discussed in this
review. Diseases showing positive result with transfer factor treatment are tabulated.
Conclusion: From this it is concluded that it is a dialyzable, active protein initiator molecule
able to transfer cell mediated immunity from healthy donor to recipient who is non-im-
mune thus keeping one away from infection.
Copyright ª2013, JPR Solutions; Published by Reed Elsevier India Pvt. Ltd. All rights
Transfer factor is a natural, non-species speciﬁc, tiny, small
peptides of 3500e6000 kDa in molecular weight, transparent,
light yellow ﬂuid having pH 6.5e7.0, composed of oligor-
ibonucleotides attached to a peptide molecule that are
inherent in all animal bodies, said to be non-allergic because
of their small size and act as immunomodulator, RNA might
provide a cytophilic property. Dr. Kirkpatrick
highly conserved region of amino acids in transfer factor that
are able to bind to the target cells with high afﬁnity. Higher
tyrosine, glycine content are present in some variants. The
ﬁrst milk in all mammalian mother called colostrums, a god’s
gift which gives passive immunity to newborn babies, has
been proven to contain transfer factor, non-antigen speciﬁc
moieties present in colostrum might contribute for the bene-
ﬁcial outcome in patients by stimulating their immune system
non-speciﬁcally and are universally effective. H. Sherwood
Lawrence demonstrated this passive transfer of immunity in
It can also be obtained from immune donor
lymphocyte who is able to transfer cell mediated immunity to
a non-immune recipient. This helps to act against bacterial,
viral, parasitic infection, autoimmune diseases, diabetes,
autism, infertility, psoriasis, retinitis pigmentosa, asthma,
The positive responses are conﬁrmed through
various tests such as delayed hypersensitivity test on skin,
response to alloantigen, speciﬁc and non-speciﬁc mitogen,
type of T cell, NK cell activity, cytokines activity. Since,
transfer factors are acquired in our bodies through natural
immune system and able to perform catalytic function in
immune system triggering effect without getting consumed,
this review aimed to provide brieﬂy its mechanism of action
once synthesized, immunological role in aiding cell mediated
immunity as it is having extraordinary beneﬁts.
Birds have transfer factor inside their eggs providing a library
of immune system and identiﬁers to make out the attacking
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drug invention today 5 (2013) 153e156
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Transfer factors are synthesized form animal,
human sources by injecting with certain pathogen to produce
speciﬁc transfer factor. Transfer factor generated using
human blood are human derived, cow and mouse spleen are
bovine, murine derived. Viza and his coworkers in 1974
observed that transfer factor with known antigenic speciﬁc-
ities can be generated from LDV/7 lymphoblastoid cell line.
The dialyzable transfer factors have onset period as hours
and able to maintain its effectiveness for ﬁve years. Transfer
factor can be puriﬁed by high performance liquid chroma-
tography and column chromatography.
3. Mechanism of action
Transfer factor lack viable cells that play a role in graft versus
host reaction, not immunogenic, contain no histocompatibil-
Natural immune response is a causative factor
for the production of transfer factor and they are produced
within T helper cells (Fig. 1), once released, the immune sys-
tem activity is inﬂuenced in several ways and studied by other
cells involved in immune system which indicates, that T
helper cells are active in ﬁghting against the pathogen,
thereby stimulating the production of new helper T cells,
Natural killer cells, macrophages, cytotoxic T cells. Thus,
marching close to the target most probably by inﬂuencing the
expression of antigen receptors on cells. Increased Th1 in turn
repress the production of Th2 and its cytokines like IL-4, IL-5,
IL-6, and IL-13. A remarkable feature of transfer factor is
eliciting multiple, opposing function
or bio feedback
mechanism by antigen speciﬁc, inducer, suppressor/regula-
tory fraction contained in it. Here, antigen speciﬁc fractions
aid the function of recognizing and memorizing pathogenic
organisms in a more faster manner. Secondly, inducer frac-
tion increases the antigenic stimulus whereas, suppressor
fraction act by releasing IL-10, an inhibitory cytokine from Th2
cells, playing a vital role in controlling immune over reactions,
mistargeted reactions in the development of autoimmune
disorders. Kirkpatrick demonstrated that in vivo administra-
tion of transfer factors to mice, afford the recipients spleen
cells with the property of responding to target antigen in vitro
by secreting gamma interferon,
a product of Th1 cells, IL-2,
TNF-alpha thereby ensuring the development of cell medi-
ated immunity. While stimulating cell mediated immunity, it
does not increases antibody secretion as well its responses
against the same speciﬁc antigen. So, transfer factors develop
cell mediated responses in patients who are suffering from
immunodeﬁcient, infectious disease, as well as in disorder
with certain anergies. Maturation of naive T cells as well as
increased cell mediated immunity are regulated by thymic
factors. It is agreed that transfer factor is more effectual in
educating naive cells about the approaching danger. So, in the
treatment of mild thymic primary immunodeﬁciency, both
thymic and transfer factors are suggested.
that decrease cell mediated immunity, Th2 supremacy are
age, cytotoxic cancer treatments, stress developed after sur-
gery, metastatic diseases.
Thus, cell mediated immunity
plays a major role in judging the morbidity and mortality
above sixty years.
4. Transfer factor and diseases
The immune system is a versatile system encompasses more
than a trillion cells, weighing about 1 kg and helps in recog-
nizing, ﬁghting, remembering invading pathogens. Each
pathogen can bring out transfer factor, atleast one transfer
factor is created for every piece of pathogen that the immune
system faces. Transfer factors inﬂuence the activities of
various immune components and also regulate cytokines.
Imbalances in the production of transfer factor lead to the
development of rheumatoid arthritis, cancer, Alzheimer’s,
heart disease, hepatitis and so on. The time taken for com-
plete development of immature immune response/delayed
hypersensitivity is 10e14 days, but transfer factor induces an
immune response in within 24 h.
IMREG I and IMREG II
help in bringing out balanced immune system. Fudenberg’s,
three important measures that have to be taken care are
antigenic speciﬁcity, strength of the extract and recipients
and also the right dose. Vetto et al reported
that patients in advanced cancer stages were not able to
respond when they were treated with antigen induced
Few diseases that were studied
with transfer factor are depicted in Table 1.
5. Stability and safety of transfer factor
Transfer factor can resist freezing, withstand treatment with
DNase, pancreatic RNase, and trypsin
but destroyed by
snake venom phosphodiesterase. No bad side effects have
been reported so far with transfer factor,
and valuable when
administered orally as well as by injection.
administration is convenient,
and easily accepted
by infants, elderly people who are at the risk for numerous
infections. Dresseler and Rosenﬁeld
reported, that heat
lability of transfer factor depends on the melting of a double
stranded nucleic acid, full activity was retained at 80 C, above
90 C destroyed the activity, had an intermediate activity at
85 C but stable to cold and consequently, able to retain its
biological activity even after storing at 20 Cto70 C forFig. 1 eShowing synthesis of transfer factor.
drug invention today 5 (2013) 153e156154
several years. Since, transfer factors are derived from blood
products it will be safe to check for HIV/AIDS/hepatitis to get
rid of blood borne diseases.
The life we are living must be healthy as long as we are.
Everyone is aware, that our immune system gets activated
only when we are exposed to infection. Hence, greater the
exposure, better the immunity. To conclude, transfer factor is
an immune enhancing molecule produced naturally by our
immune system aiding immunological memory of recipient. It
is not a drug or vitamin to cure our illness but it acts as a
channel to our immune system. So, a balanced immune sys-
tem is attained. Eventhough, they found to be useful, the
success rate varies depending upon the preparation of trans-
fer factor, the right dose selected, the potency, the degree of
illness and duration of infection.
Conﬂicts of interest
The author has none to declare.
The author whole heartedly thank JPR solution for their partial
contribution in publishing this article without which this
would have not been possible.
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Diseases showing positive result on
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Osteosarcoma Increased cell mediated cytotoxicity Fudenberg 1976
Varicella with acute leukaemia in children Steele et al, 1980
Herpes simplex virus Improved T cell function Steele et al, 1976
Viza et al, 1986
WiskotteAldrich syndrome Increased C3 level returned to normal, no new infection,
absence of eczema
Levin et al, 1970
Glioma Reduces the tumour size, and increases CD2þ, CD4þ,
CD8þand NK cell counts, apoptotic tumour cells
Pineda et al, 2005
Prostate cancer Higher survival rates Pizza et al, 1996
HIV Increased levels of helper T cells and cytotoxic T cells Granitov et al, 2002
Lung cancer Longer survival Pilotti et al, 1996
Hepatitis C Stimulates Th1, which helps in clearing of viral particles
Chronic mucocutaneous candidiasis Restored cellular immunity
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